Management of severe hypercholesterolemia in italy: evidence from santorini study

Abstract The management of severe hypercholesterolemia (sHC) (LDL–C >160 mg/dL) represents a clinical challenge in routine practice, mainly in the setting of high cardiovascular (CV) risk. The aim of the present analysis was to assess the characteristics and management at baseline examination of patients with sHC enrolled in the Italian cohort of SANTORINI study. The SANTORINI study (NCT04271280) is a multinational, observational, prospective study evaluating the use of lipid–lowering therapies (LLTs) in 9044 adult patients with high– and very–high CV risk enrolled from 14 European countries between March 2020 and February 2021, with a 12–month follow–up period per patient. The Italian cohort comprised 1977 patients, 229 (11.6%) of whom were classified with sHC. Their mean age was 59.4 years, 56% were male, BMI was 27.2 kg/m2 and mean LDL–C levels were 196.7 mg/dL. In 7% of cases sHC was reported to be associated with a clinical diagnosis of familial hypercholesterolemia. By investigators, 150 (65.5%) patients were classified at very–high and 79 (34.5%) at high CV risk, mainly (74.2%) based upon ESC/EAS European guidelines criteria. Atherosclerotic cardiovascular disease was actually present in 68.4% of patients, while 40.6% were on primary prevention. Despite sHC was associated with high CV risk, 64.6% of patients had no documented LLTs at baseline, 15.3% was receiving lipid–lowering monotherapy including 9.2% on statins (6.1 % moderate and 2.6% high–intensity), 1.7% were on ezetimibe, 1.6% on PCSK9i and 0.5% on other oral LLTs, and 20.1% was receiving combination therapy (10.9% were on statin + ezetimibe, 4.8% on PCSK9i + oral LLT, and 4.4% other oral combination therapy). Based on present findings, it is therefore concluded that, although the clinicians mostly follow current guidelines to determine CV risk in hypercholesterolemia, there is a low utilisation of LLTs, especially combination therapies, in the subgroup of patients with sHC at high and very–high CV risk. This means that further measures are needed to improve the therapeutic management of these patients in order to minimise the risk of adverse cardiovascular events.